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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
22 March 2010 - 05 April 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: - JMAFF, 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: liquid stored at room temperature.
Details on test material:
- Name of test material (as cited in study report): PAX-XL9
- Name of substance NOTOX: 202028/A
- Substance type: Clear colourless liquid (determined at NOTOX)
- Physical state: Liquid.
- Analytical purity: 17.9% , Al = 4.4%
- Lot/batch No.: 87T1-170909
- Expiration date of the lot/batch: 18 December 2010 (allocated by NOTOX, 1 year after receipt of the test substance)
- Stability under test conditions: Stable under storage conditions.
- Storage condition of test material: At room temperature in the dark
- Other:
Density: 1.189 kg/L at 21°C
pH: 3.0 ± 0.5% (20°C)

Test animals

Species:
rat
Strain:
other: Crl:WI(Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals were selected (approximately 10 weeks old).
- Weight at study initiation: body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: No.
- Housing:
Before exposure
Group housing of five animals per sex per cage in labelled Macrolon cages (type IV; height 18 cm) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
After exposure
Group housing as described above, except that a paper sheet was introduced into the cage covering the bedding and cage enrichment to prevent suffocation in case of bad health condition. At the end of the Day of exposure the paper sheet was removed.
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) except during exposure to the test substance.
- Water (e.g. ad libitum): Free access to tap water except during exposure to the test substance.
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.
- Health inspection: A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health

Animals 4 and 5 were replaced by spare animals, 30 minutes after start of exposure, and exposed immediately after restraining. The animals were not acclimatised for at least 15 minutes. The animals were replaced since the original animals were found dead during exposure, possibly caused by stress due to restraining. Since the exposure was ongoing, it was not possible to acclimatise the animals to restraining. It was considered that this event did not affect the exposure results for these animals.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 – 21.7°C
- Humidity (%): 42 - 60%
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 22 March 2010 To: 05 April 2010

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle).
Details on inhalation exposure:
The design of the exposure chamber is based on the flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983). The chamber consisted of three animal sections with eight animal ports each. Each animal port had its own atmosphere inlet and exhaust outlet. The animals were placed in restraining tubes and connected to the animal ports. The number of animal sections and number of open inlets were adapted to the air flow in such a way that at each animal port the theoretical air flow was at least 1 L/min, which ensures an adequate oxygen supply to the animals. The main inlet of the test atmosphere was located at the top section and the main outlet was located at the bottom section. The direction of the flow of the test atmosphere guaranteed a freshly generated atmosphere for each individual animal.
The placement of the individual animals in the inhalation chamber is shown in figure 2. All components of the exposure chamber in contact with the test material were made of stainless steel, glass, rubber or plastic. To avoid exposure of the personnel and contamination of the laboratory the exposure chamber was placed in a fume hood, which maintained at a slight negative pressure.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
1.6 mg/L, corresponding to 6.1 mg/L of the neat test substance (correction factor 3.7 for the evaporable water content).
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
202028/A was administered as an aerosol by inhalation for 4 hours to one group of five male and five female Wistar rats. Animals were subjected to daily observations and determination of body weights on Days 1, 2, 4, 8 and 15. Macroscopic examination was performed after terminal sacrifice (day 15).
Statistics:
No data.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred.
Clinical signs:
Clinical signs observed among most animals after exposure included lethargy, hunched posture and/or piloerection on Days 1 and/or 2. No clinical signs were observed during exposure.
Body weight:
Mean body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
None.

Any other information on results incl. tables

None.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the inhalatory LC50, 4h value of 202028/A (aerosol) in rats was considered to exceed 5 mg/L. Therefore, no classification is required according to EU criteria.
Executive summary:

In an acute inhalation toxicity study performed according to OECD Guideline 403 and in compliance with GLP, groups (5/sex/dose) of Wistar rats were given 202028/A as an aerosol by inhalation for 4 hours at 6.1 ± 1.8 mg/L of the neat test substance (correction factor 3.7 for the evaporable water content).

Animals were then observed for mortality, clinical signs and body weights for 14 days and were all sacrificed for macroscopic examination (Day 15).  

  

No mortality occurred. Clinical signs observed among most animals after exposure included lethargy, hunched posture and/or piloerection on Days 1 and/or 2. No other clinical signs were observed during exposure. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

Under the test conditions of this study, the inhalatory LC50, 4h value of 202028/A (aerosol) in rats was considered to exceed 5 mg/L. Based on these results, no classification is required according to EU criteria.